Cytokine Involvement in Central Nervous System Disease

[[abstract]]©1995 Blackwellpublishing - Cytokines constitute a large group of soluble mediators possessing a spectrum of biological activities influencing hematopoiesis, immune responses, and cellular communication. There is now convincing evidence that cytokines are important mediators in bidirectional regulatory circuits between the immune system and the CNS and, as in the periphery, act as multifunctional effectors in the CNS.3-5 The expression of various cytokines or their genes is altered in the brain in a variety of CNS diseases such as multiple ~clerosis,~ac.q~u ired immunodeficiency syndrome (AIDS) encephalitis,*-" Alzheimer's disease,"." ~crapie,a'~nd viral15 or bacterial infection.16 Production of cytokines within the CNS may arise from multiple sources including infiltrating mononuclear cells such as T cells and macrophages and also from resident neural cells, particularly the astrocytes and microglia. the ability of the glial cells to produce a variety of cytokines, including, IL-1, IL-6, IFN-a, TNF-a, and TGF-p,'9-23 suggests the existence of a CNS-cytokine network. The CNS-cytokine network likely plays a major role in coordinating a diversity of intraneural responses that, although primarily aimed at protecting the host, may become spatially and temporally dysregulated leading to the inappropriate production of the cytokines. Under these circumstances and given their potent biological activities, it has been proposed that cytokines may be harmful to the host, contributing to tissue injury within the CNS.3.18*2W4 hether in diseases where they are expressed, such as AIDS encephalitis, Alzheimer's disease, or multiple sclerosis, cytokines are indeed primary neuropathogenic mediators remains a largely unknown but important question- especially given the possibility for therapeutic intervention. Recent studies in our laboratory have focused on this question by utilizing a transgenic approach to direct the constitutive expression of cytokines such as IL-6 to astrocytes in the CNS of mice. the findings that will be discussed here suggest that these mediators possess the potential to induce a broad spectrum of structural and functional CNS impairments giving rise to frank neurodegenerative disease.[[fileno]]2060208010021[[department]]醫環